Baby Rats Born From Mice

John Roach
for National Geographic News
August 30, 2006
Rat sperm cells grown in mouse testicles have been used to successfully produce healthy baby rats, scientists say.

The research proves a concept first envisioned a decade ago: that functional sperm cells from many types of animals can be produced in small surrogate fathers of a different species.

The finding has implications for species conservation as well as farming and agriculture.

"If you use a surrogate father, you can reduce the space for keeping animals and the amount of food [required]," Takashi Shinohara, a molecular geneticist at Kyoto University in Japan, said in an email.

Frozen sperm stem cells could be used to fertilize eggs of endangered species or to create genetically modified organisms more easily.

And cattle producers could save space and food by growing bull sperm in mice. (Related: "Mice Used as Sperm Factories for Pigs, Goats" [August 2002].)

Shinohara is lead author of the study, published yesterday in the journal Proceedings of the National Academy of Sciences (PNAS).

Rats and Mice

Sperm stem cells are incapable of fertilizing eggs themselves but give rise to cells that develop into sperm.

Scientists have known since 1996 that rat sperm stem cells transplanted into mouse testicles produced what appeared to be viable rat sperm.

However, the technology to show that these rat sperm actually worked as advertised was lacking until now.

Shinohara and his colleagues used a recently developed technique called in vitro microinsemination to fertilize rat eggs with mouse-grown rat sperm.

In the laboratory technique, researchers inject sperm cells next to the egg to enhance the chances of fertilization.

Successfully fertilized eggs are then transferred into females.

Of the 339 eggs transferred by the research team, 90 managed to implant properly in the uterus, and 15 offspring were born.

"The offspring grew up to be fertile adults and showed no apparent abnormalities," the researchers write in PNAS.

Since the researchers could only inject sperm near a limited number of eggs per day, they froze some of the sperm for injection on later days.

All 15 offspring were derived from freeze-thawed sperm, the researchers note.

"I assume that the freeze-thaw procedure somehow selected normal rat sperm," Shinohara said. "Other fragile sperm, although they may look normal, probably could not stand the freeze-thaw procedure."

Proof of Concept

Ina Dobrinski, director of the Center for Animal Transgenesis and Germ Cell Research at the University of Pennsylvania Medical School in Kennett Square, says the study is a nice proof of concept.

"We knew we could make rat sperm, but we didn't know for sure if they would do what sperm do—i.e., make a baby," she said. "The question needed to be answered."

Dobrinski doubts, however, that the technique is widely applicable to other species.

Previous research has shown that cells from species other than rodents cannot make sperm when transplanted to mouse testicles, she says.

"Everybody asks, what about people? Can we make human sperm in a mouse and get a fertilized human egg?" she said.

"The answer resoundingly—even after this paper—is no, and that may actually be a good thing."

(See an overview of human genetics.)

Research Implications

According to Kyoto University's Shinohara, the use of small surrogate animals may be beneficial for future experiments designed to understand how specific genes function. The technique could also be used to create genetically modified animals.

Researchers have access to sperm stem cells for several animal species, but altering the cells and using them to produce genetically modified offspring of large animals such as cattle requires a lot of space and time, Shinohara says.

"In this sense, the surrogate father strategy can be very useful for transgenic or knockout experiments," he said.

In knockout experiments, scientists inactivate or "knock out" a gene to observe its effect on an animal and determine how the gene works.

Ultimately, scientists could grow sperm with desirable genetic traits in surrogate animals, Shinohara says.

The finding also has potential for species conservation.

"With the current procedure, you can retrieve [sperm] stem cells from an endangered species, make frozen stocks after expansion of stem cells, thaw them, and put them into surrogates to produce sperm, which can be used to create an embryo," he explained.

Dobrinski, of the University of Pennsylvania, adds that since the applicability of this technique to animals other than rats is still unproven, scientists have time to weigh the ethical implications of the technique before beginning such procedures.

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